The production of beta-lactamase (penicillinase) enzymes by bacteria is still an important factor in bacterial resistance to penicillin therapy and seems to be coming more so with the movement by conjugation of plasmids coding for beta-lactamases into previously non-producer species e.g., N. gonorrhoeae. Despite considerable effort few general inhibitors of these enzymes are yet available. The objective of the proposed research is to examine in detail the mechanism of action of a recently discovered, potent active-site directed, irreversible beta-lactamase inhibitor, 6-beta-bromo-penicillanic acid, and a variety of its analogs. Such studies, carried out also with a variety of beta-lactamases, should lead to a better idea of the mechanism of the beta-lactamase action of these enzymes and to a broader view at the active-site level of the variation of these enzymes among bacterial species. It is hoped that the work might also lead to a clinically useful general inhibitor. Finally, it is proposed that an investigation of the interaction of these inhibitors with bacterial cell wall components could lead to results bearing on the questions of beta-lactamase evolution, the mechanism of antibiotic action of penicillins and the relationship between these.